In my laboratory, we focus on two major areas of research: (1) studying the neural mechanisms of olfactory coding and the behaviors it triggers, and (2) developing new techniques for imaging neuronal activity and cell type identification.
Olfaction is distinguished among sensory systems by being shallow but broad. It is shallow because there are relatively few stages of “preprocessing” needed before interacting with brain areas involved in innate and learned behaviors; it is broad due to the diversity of inputs stemming from the hundreds or thousands of olfactory receptor genes that detect odors. Historically, this diversity posed a challenge to sensory physiologists. We pioneered the use of light sheet microscopy for calcium imaging, and were the first to image from tens of thousands of neurons simultaneously and now routinely record exhaustively from the entire sensory input repertoire. In more recent work, we have coupled high-throughput imaging technologies with optical tagging and gene sequencing to develop a new technique, PhOTseq, for identifying gene expression from functionally-defined cell types. These new tools allow us to exploit the diversity of inputs in olfaction as an advantage: natural sensory cues provide us with a “ligogenetic toolkit” permitting exquisite control over activation of a large number of distinct pathways.
Scientifically, some of our major discoveries include the identification of mouse pheromones and some of the natural behaviors they trigger, elucidation of mechanisms of sensory integration in the accessory olfactory bulb, discovery of mechanisms for individuality and plasticity in early sensory perception, and a deeper understanding of the relationship between sequence and function in olfactory receptors. Dr. Holy is also among the world’s foremost creators of Julia, a programming language designed for both ease-of-use and high performance whose adoption is growing exponentially. Ongoing work includes many of these areas as well as new initiatives in technology development, olfactory navigation, learning and memory, computation, and machine learning.
- Meeks JP, Arnson HA, and Holy TE. Representation and transformation of chemosensory information in the mouse accessory olfactory system. Nature Neuroscience. 2010 13: 723-730.
- Turaga D and Holy TE. Image-based calibration of a deformable mirror in wide-field microscopy. Applied Optics. 2010 49: 2030-2040.
- Nodari F, Hsu F-F, Fu X, Holekamp TF, Kao L-F, Turk J, Holy TE. Sulfated steroids as natural ligands of mouse pheromone-sensing neurons. J. Neuroscience. 2008 28: 6407-6418.
- Holekamp TF, Turaga D, Holy TE. Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy. Neuron. 2008 57: 661-672.
For a complete list of Dr. Holy's publications, click here.